Verapamil (1) is presently in clinical use as a racematic for the treatment of hypertension, angina, atrial fibrillation and paroxysmal supraventricular tachycardia. However, constipation is a well known and undesirable side effect of this drug with a reported incidence up to 38% of all patients treated; see C. Yedinak, American Pharmacy (1993) NS 33:8; 49-66. This can result in reduced compliance or even cessation of treatment. ##STR1##
The opposite enantiomers of verapamil have different biological activities and different potencies. The pharmacological profile is determined by stereoselectivity of pharmacodynamics and pharmacokinetics.
The (R)-enantiomer may be of benefit for the reversal of multi-drug resistance in cancer chemotherapy (see Eliason, Int. J. Cancer (1990) 46: 113).
The (S)-enantiomer may be of benefit in the treatment of atrial fibrillation (see Raschack, Naunyn-Schmiedeburg's Arch Pharmacol. (1976)294: 285-297). It may also be of benefit in the treatment of angina (see Curtis et al., Br. J. Phamac. (1986)89: 137-147), although dose-limiting side effects are reported to be associated with its use, such as depression in myocardial activity (see Satoh et al, Journal of Cardiovascular Pharmacology (1980)2: 309-318) and atrioventricular (AV) conduction block (see Raschack, as above).